![]() To varying degrees, however, these studies included patients with other forms of VHD. ![]() All of the pivotal trials comparing VKAs with the NOACs in AF (13–16) have excluded patients with AF in the setting of moderate or severe mitral stenosis or with mechanical prosthetic valves, a group considered at particularly high risk of thromboembolism. There is, however, uncertainty over antithrombotic prophylaxis in patients with coexisting VHD and AF, a condition often referred to as “valvular AF,” but that is poorly defined by clinicians and investigators (5,12). The availability of non-VKA oral anticoagulants (NOACs) since 2009 has increased the number of AF patients treated with anticoagulants for stroke prevention (11). Vitamin K antagonists (VKAs) were, for many years, the mainstay of thromboprophylaxis in AF (8–10). Valvular heart disease may be associated with an increased incidence of AF because of enlargement of the left atrium (7). Risk factors for both conditions include advanced age, hypertension, diabetes, coronary heart disease, and heart failure. Even after adjusting for other relevant concomitant conditions, VHD is associated with a 1.8- to 3.4-fold higher risk of AF in men and women, respectively (6). ![]() Both VHD and AF are independent causes of mortality and morbidity, including a heightened risk of stroke and other thromboembolic events (2,4). Valvular heart disease (VHD) and atrial fibrillation (AF) are common conditions (1–4) and often coexist, especially in the elderly (5). Adverse event (excluding bleeding) and discontinuation rates were similar among the three treatment groups. Warfarin therapy was proactively monitored throughout the trial, resulting in a median time within therapeutic range (TTR) of 68.4%. Complete information on the primary endpoint was ascertained for 99.5% of the total 56,346 patient-years of potential follow-up with only one patient lost to follow-up. The principal safety outcome was adjudicated major bleeding. The primary efficacy outcome was the time to first adjudicated stroke or SEE. Edoxaban dosage was reduced by half if any of the following was present at randomization or during the course of the study: creatinine clearance 30-50 mL/min, bodyweight < or = 60 kg or concomitant verapamil, quinidine or dronedarone (standard dosing was resumed if the concomitant drug was discontinued and no other dose reduction factors were present). Patients were randomized (1:1:1) to receive warfarin (n = 7,036), edoxaban 60 mg (n = 7,035) or edoxaban 30 mg (n = 7,034). In addition, we specifically designed a comprehensive transition plan to protect patients from the undue risk of stroke and bleeding when switching to open-label anticoagulation at the end of the trial." "In conducting this landmark trial, we sought to provide clinicians with robust data, evident by the trial size and follow-up, high percentage of time in therapeutic range for the warfarin treatment arm and very low rate of missing data. In addition, we identified an appropriate dose regimen for patients with clinical factors such as renal impairment and low body weight," said Robert Giugliano, M.D., S.M., FAHA, FACC, senior investigator, TIMI Study Group, physician cardiovascular medicine, Brigham and Women's Hospital, associate professor of medicine, Harvard Medical School, and co-global lead investigator, ENGAGE AF-TIMI 48 trial. "The results from the ENGAGE AF-TIMI 48 trial showed that edoxaban may provide a new treatment option for the prevention of stroke or systemic embolic events that demonstrates comparable efficacy to warfarin, while significantly reducing the risk of major bleeding.
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